Single‐Cell Hyperthermia: Diamond Quantum Thermometry Reveals Thermal Control of Macrophage Polarization

Abstract

Abstract Fever elevates body temperature to enhance immune response; however, intracellular temperature can fluctuate by up to 15 °C, suggesting a previously unrecognized layer of thermal regulation. While hyperthermia has long been exploited in medicine, how localized temperature gradients influence cellular fate remains poorly understood. Here, a dual‐function nanodiamond platform is introduced that integrates optically detected magnetic resonance (ODMR) thermometry with croconium‐dye‐based photothermal heating to precisely modulate temperature within endo‐lysosomal compartments of macrophages. Controlled intracellular hyperthermia triggers oxidative stress, transcriptional reprogramming, and polarization toward a pro‐inflammatory phenotype, as confirmed by immunofluorescence, flow cytometry, and transcriptomics. These findings reveal intracellular thermal gradients as active regulators of immune signaling and gene expression. By establishing a direct subcellular thermal trigger for immune activation, independent of the canonical heat‐shock pathway. This work introduces a quantum‐enabled strategy for probing and programming cellular thermodynamics at the nanoscale.